👤 Carlo Gaetano

Intermittent hypoxia is a key factor in inducing chronic systemic inflammation in obstructive sleep apnea (OSA), providing the molecular substrate for the development of a range of associated diseases. Variations in blood oxygen levels are known to cause epigenetic changes, including modulation of non-coding RNAs. We sought to investigate whether selected hypoxia-associated non-coding RNAs, i.e. miR-210-3p, miR-139-3p, MALAT1, and BACE1-AS, could be modulated by ventilatory therapy with continuous positive airway pressure (CPAP) in patients with moderate to severe OSA. Their relationships with respiratory indices was also evaluated. Peripheral blood was collected from 68 patients with OSA before (pre-CPAP group) and after a 6-month treatment with CPAP (post-CPAP group). Circulating microRNAs and long non-coding RNAs levels were measured by real-time qPCR. Respiratory indices during sleep were evaluated by polysomnography. Following CPAP, levels of miR-210-3p, MALAT1, and BACE1-AS decreased while those of miR-139-3p increased (P<0.05 for all). Correlations between non-coding RNAs and ventilatory indices before CPAP, particularly time below 90 % of oxygen saturation during sleep, were statistically significant (P<0.05 for miR-210-3p, MALAT1, and miR-139-3p). Interestingly, all correlations were abolished by ventilation therapy. We conclude that CPAP therapy can modulate hypoxia-associated non-coding RNAs by restoring adequate blood oxygen levels, with potential effects on target gene expression. We speculate that non-coding RNAs may play a role in the development of OSA-related disorders such as cancer and cognitive diseases. Show less

The brains of teleost fish show extensive adult neurogenesis and neuronal regeneration. The patterns of gene regulation during fish brain aging are unknown. The short-lived teleost fish Nothobranchius furzeri shows markers of brain aging including reduced learning performances, gliosis, and reduced adult neurogenesis. We used RNA-seq to quantify genome-wide transcript regulation and sampled five different time points to characterize whole-genome transcript regulation during brain aging of N. furzeri. Comparison with human datasets revealed conserved up-regulation of ribosome, lysosome, and complement activation and conserved down-regulation of synapse, mitochondrion, proteasome, and spliceosome. Down-regulated genes differ in their temporal profiles: neurogenesis and extracellular matrix genes showed rapid decay, synaptic and axonal genes a progressive decay. A substantial proportion of differentially expressed genes (~40%) showed inversion of their temporal profiles in the last time point: spliceosome and proteasome showed initial down-regulation and stress-response genes initial up-regulation. Extensive regulation was detected for chromatin remodelers of the DNMT and CBX families as well as members of the polycomb complex and was mirrored by an up-regulation of the H3K27me3 epigenetic mark. Network analysis showed extensive coregulation of cell cycle/DNA synthesis genes with the uncharacterized zinc-finger protein ZNF367 as central hub. In situ hybridization showed that ZNF367 is expressed in neuronal stem cell niches of both embryonic zebrafish and adult N. furzeri. Other genes down-regulated with age, not previously associated with adult neurogenesis and with similar patterns of expression are AGR2, DNMT3A, KRCP, MEX3A, SCML4, and CBX1. CBX7, on the other hand, was up-regulated with age. Show less